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Biomedical subjects

C Peck

Publications and source records attributed to C Peck.

46 records · Page 3Linked to original sources
PubMed1981

Effect of methotrexate and 1-beta-D-arabinofuranosylcytosine on pools of deoxyribonucleoside triphosphates in L1210 ascites cells.

Pools of deoxyribonucleoside triphosphates in L1210 cells were assayed for drug-induced changes that might indicate the metabolic basis for retention of 1-beta-D-arabinofuranosylcytosine triphosphate by these cells after treatment with methotrexate (MTX) and 1-beta-D-arabinofuranosylcytosine (ara-C). Within 20 min after treatment with MTX, the pool of deoxythymidine triphosphate (dTTP) had decreased by about 50% and during the next 8 hr decreased slowly to 30% of its initial level. When MTX-induced decreases in the cellular contents of deoxycytidine triphosphate (dCTP), deoxyadenosine triphosphate (dATP), and deoxyguanosine triphosphate (dGTP) were normalized to percentages of the initial levels, they coincided with the second slower phase of decrease in dTTP. During the study, levels of both dTTP and dCTP remained constant in cells from mice treated with 0.9% NaCl solution, whereas levels of both dATP and dGTP decreased. MTX caused a significantly more rapid decrease in the level of dATP than did 0.9% NaCl solution but not in the level of dGTP. Over a 9-hr period, after injection of ara-C, levels of both dTTP and dCTP doubled while levels of both dATP and dGTP remained unchanged. When ara-C and MTX were administered together, levels of dTTP, dATP, and dGTP did not change significantly, and the increase in dCTP was only 25% of the increase after treatment with ara-C alone. Thus, the most striking change in deoxyribonucleoside triphosphate pools after combined administration of MTX and ara-C was an increase in dCTP concentration that reached about one-fourth the concentration achieved with ara-C alone. We suggest that MTX, by attenuating the ara-C-induced increase in dCTP, caused a change in the allosteric regulation of either deoxycytidine kinase or deoxycytidylate deaminase (or both), thereby potentiating the activity of ara-C.

Animals↗
PubMed1979

Serum levels of methotrexate by the ligand-binding assay after "high-dose" therapy for osteosarcoma.

The method of Arons et al. (Cancer Res. 35:2033-2038, 1975) for assaying methotrexate (MTX) was used to monitor serum levels of the drug attained in 18 patients with osteosarcomas. The patients received either 100 mg or 200 mg of MTX/kg via a 6-hour infusion. With one fatal exception, unacceptable toxicity to MTX was prevented by leucovorin. Serum levels of the drug were assayed routinely at 6, 12, and 18 hours after termination of the infusion. Although significantly higher serum levels of MTX were observed at 6 hours after the infusion of 200 mg MTX/kg than after 100 mg/kg, the variation in rate of clearance of individual patients masked any subsequent dosage-related differences. The mean half-time for clearance of MTX was similar irrespective of the dosage of MTX and was 2.91 +/- 1.51 hr for 53 treatments. The single incidence of toxicity, requiring hospitalization, was accompanied with markedly higher serum levels of MTX at 18 hours, but not at either 6 or 12 hours after termination of the drug infusion, and by a slightly slower rate of clearance, 6.2 hours. Certain minor adaptations were incorporated in the original assay to simplify the analysis of data.

Drug Therapy, Combination↗
PubMed1979

Methotrexate-induced changes in the levels of 1-beta-D-arabinofuranosylcytosine triphosphate in L1210 cells.

Treatment with methotrexate (MTX) plus 1-beta-D-arabinofuranosylcytosine (ara-C) on Days 1, 4, and 7 after i.p. inoculation of L1210 ascites cells was more effective than treatment with one drug on Days 1, 4, and 7 followed by the second drug on Days 2, 5, and 8. Simultaneous treatment with both drugs was associated with a retention of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) but no increase in the activity of deoxycytidine kinase in L1210 cells, whereas pretreatment with MTX 24 hr before the administration of ara-C was associated with approximately 2-fold increases in the level of ara-CTP and of deoxycytidine kinase in L1210 cells. However, from 5 hr after treatment with ara-C, higher levels of ara-CTP were observed in L1210 cells treated simultaneously with both drugs than in cells from animals pretreated with MTX 24 hr before treatment with ara-C. The superiority of simultaneous treatment over sequential treatment and the synergism between MTX and ara-C, previously reported for this schedule of simultaneous treatment, are attributed in part to the MTX-induced retention of ara-CTP and the increased exposure of L1210 cells to ara-CTP that results from the slower clearance of ara-CTP.

Animals↗
PubMed1978

The effect of EMG biofeedback on postoperative pain following abdominal surgery.

To investigate the effects of electromyography (EMG)-biofeedback on pain experienced during the immediate post-operative period following abdominal surgery, twelve patients were randomly assigned to either (1) EMG-biofeedback from abdominal muscles; (2) EMG-biofeedback from the frontalis muscles; or (3) were given no EMG treatment. EMG training consisted on one pre-operative 30 minute session, and three 30 minute postoperative sessions. All patients were able to reduce EMG activity. A within-sessions analysis of pain reports (on a 0-10 pain intensity scale) indicated that EMG biofeedback is an effective method of pain relief only when feedback is given to the muscle site involved in the operation.

Abdomen↗
PubMed1975

Improved computer-assisted digoxin therapy. A method using feedback of measured serum digoxin concentrations.

Automated feedback control methods were applied to a medical problem, in a computer program that used measured serum digoxin concentrations (as feedback) to predict future concentrations and to achieve desired concentrations. The system was validated by comparing its ability with the corresponding ability of physicians to regulate digoxin dosage. The prospective, randomized study included 51 patients. In the presence of varying amounts of feedback (serum digoxin concentration) information, the computer always predicted future digoxin concentrations as accurately as did physicians. For both computer and physician, the decrease in the prediction errors when two concentrations were known against that when no concentrations were known was significant: mean absolute error decreased from 0.40 to 0.25 ng/ml for the physicians and from 0.45 to 0.27 ng/ml for the computer. Thus the computer system is capable of simulating and reproducing a sophisticated aspect of physician behavior: "learning" about individual patient responses. The computer achieved desired concentrations more accurately than did physicians, especially when two or more previous digoxin concentrations were abailable (mean absolute achievement error for computer, 0.28 ng/ml; for physicians, 0.50 ng/ml).

Achievement↗